Our long term goal of this proposal is to study the molecular events leading to the progression of breast cancer with emphasis on the role of elk-1 gene. Previously we observed increase in the expression of elk-1 RNA in the presence of estrogen in breast cancer cells. Recently, we have studied and have found no significant effect of estrogen on the transcriptional activation and expression of elk-1 protein, suggesting that the estrogen regulation of elk-1 could be at the level of transcription. Previously, we found BRCA1 gene product to function as a regulator of elk-1 gene. We have developed human breast cancer cell lines expressing BRCA1. Our results demonstrate BRCA1 to function as an inducer of apoptosis. These results suggest that BRCA1 and elk-1 genes may play a critical role in the regulation of apoptosis. Thus a wide variety of human malignancies like breast cancers have a decreased ability to undergo apoptosis. This could be due to lack/decreased levels of functional BRCA1 proteins. Treatments that are aimed at increasing the apoptotic threshold by BRCA1 gene therapy may have the potential to prevent the progression of these malignancies.